Perspectives on the Efficacy of Antidepressants for Child and Adolescent Depression

P ractitioners of pediatric medicine may still be undecided as to whether the newer generation of antidepressant drugs is effective for child and adolescent depression (CAD) [1]. Since 1989, when selective serotonin reuptake inhibitors (SSRIs) were introduced in the United States, they have become the top-selling drug category; as many as one in eight adult Americans having tried at least one SSRI in the past ten years. Despite their popularity in treating adult depression, the effi cacy of SSRIs for CAD remains in dispute. In this article, I examine some of the core problems in medical research that have led to this disagreement. Advances in molecular biology and neuroscience have fostered increasingly specifi c drugs. However, the pharmaceutical industry promotes an idea of drug specifi city that may extend beyond the existing data. For example, SSRIs may selectively block the reuptake of serotonin, as claimed by many SSRI manufacturers, but they also infl uence numerous postsynaptic serotonin receptor systems, instigating multiple neurochemical effects. Furthermore, certain neurotransmitter systems are so tightly entwined that affecting one inevitably infl uences others (e.g., selective norepinepherine reuptake inhibitors also infl uence the serotonergic system). Hence, drugs often have effects that seem unrelated to the presumed therapeutic outcome (e.g., tricyclic antidepressants [TCAs] and SSRIs have signifi cant effects on fast sodium channels and platelet function, respectively). And one drug can treat a variety of syndromes. For example, SSRIs are effective for symptoms ranging from obsessive-compulsive disorder to panic and anxiety. Thus, specifi city, as defi ned by the pharmaceutical industry, is perhaps an overextended notion. Antidepressant medications have become central to managing CAD [2]. Because double-blind trials of TCAs have failed to show greater effi cacy than placebo for treating CAD [3,4], and concerns have been raised about the side effects of TCAs, SSRIs have been seen as the viable option for treating CAD [5]. Indeed, the 21st century ushered in major clinical guidelines endorsing SSRIs as fi rst-line pharmacotherapy for CAD in both North America and the United Kingdom [6,7]. Most rigorous studies that tested the safety and effi cacy of these medications in depressed adolescents began after these drugs were deemed " fi rst line " by the professional community of child and adolescent psychiatrists. Yet the recent history of SSRIs is replete with inconsistent verdicts about their safety. For example, in January 2003, the US Food and Drug Administration (FDA) approved fl uoxetine …